Pulmonary Fibrosis in Hermansky-Pudlak Syndrome

Abstract

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive genetic disorder characterized by oculocutaneous albinism and a bleeding diathesis due to platelet dysfunction. More than 50% of cases worldwide are diagnosed on the Caribbean island of Puerto Rico. Genetic testing plays a growing role in diagnosis; however, not all patients with HPS have identified genetic mutations. In Puerto Rico, patients with HPS are often identified shortly after birth by their albinism, although the degree of hypopigmentation is highly variable. Ten subtypes have been described. Patients with HPS-1, HPS-2, and HPS-4 tend to develop pulmonary fibrosis in Puerto Rico; 100% of patients with HPS-1 develop HPS-PF. HPS-PF and idiopathic pulmonary fibrosis are considered similar entities (albeit with distinct causes) because both can show similar histological disease patterns. However, in contrast to idiopathic pulmonary fibrosis, HPS-PF manifests much earlier, often at 30-40 years of age. The progression of HPS-PF is characterized by the development of dyspnea and increasingly debilitating hypoxemia. No therapeutic interventions are currently approved by the U.S. Food and Drug Administration for the treatment of HPS and HPS-PF. However, the approval of two new antifibrotic drugs, pirfenidone and nintedanib, has prompted new interest in identifying drugs capable of reversing or halting the progression of HPS-PF. Thus, lung transplantation remains the only potentially life-prolonging treatment. At present, two clinical trials are recruiting patients with HPS-PF to identify biomarkers for disease progression. Advances in the diagnosis and management of these patients will require the establishment of multidisciplinary centers of excellence staffed by experts in this disease.

Targeted resequencing reveals genetic risks in patients with sporadic idiopathic pulmonary fibrosis

“…Additionally, a common polymorphism (rs35705950) in the promoter of MUC5B is significantly more prevalent in individuals with both sporadic and familial IPF (Peljto et al., ; Zhu et al., ). Importantly, pulmonary fibrosis can occur in some rare genetic disorders such as dyskeratosis congenita, Hermansky‐Pudlak syndrome (HPS), and tuberous sclerosis, indicating a shared genetic pathogenesis (Hisata et al., ; Islam & Roach, ; Vicary, Vergne, Santiago‐Cornier, Young, & Roman, ). Current data suggest that at least one‐third of the sporadic and familial IPF can be explained by common genetic variants identified in large GWASs, some of the variants differ in different populations, some associated with disease prognosis or response to treatment (Fingerlin et al., ).…”

Hermansky-Pudlak syndrome with a novel genetic variant inHPS1and subsequent accelerated pulmonary fibrosis: significance for phenocopy diseases

“…WAG:  Approximately 75% of the HPS population will die of causes directly related to the condition, in particular pulmonary fibrosis, haemorrhagic episodes and granulomatous colitis 3. Clinical manifestations of HPS-associated pulmonary fibrosis classically occur in the fourth or fifth decades of life.…”

“…OJMcE: Lung transplantation is the only definitive treatment for HPS-associated pulmonary fibrosis and has been performed in subtypes 1, 2 and 4 3. Several challenges exist with respect to this option.…”

Heŕmanský–Pudlák syndrome: A case report

“…Lung biopsy not indicated due to bleeding diathesis. New antifibrotic drugs, pirfenidone and nintedanib have identified capable of reversing and ameliorate progression of pulmonary fibrosis and lung transplant is life prolonging treatment [24]. Oral pirfenidone for the pulmonary fibrosis of Heřmanský-Pudlák syndrome clinical trial is ongoing National Human Genome Research Institute (NHGRI) since 1999.…”

“…They have shown no benefit in milder disease of HPS 1 and HPS 4. Gene transfer for potential correction of BLOC-3 dysfunction needs more further studies and research [24]. Infliximab is useful in cases of HPS colitis.…”